AND+ isocitrate dyhdrogenase (AND+ IDH; EC 1.1.1.41) is a key step in the citric acid cycle and catalyzes the oxidative decarboxylation of isocitrate to form .alpha.-ketoglutarate, CO.sub.2, and NADH. Its key regulatory role in the TCA cycle is well documented. Traditionally the enzyme was also considered to be responsible for the production of 2-oxoglutarate which is a precursor in ammonia assimilation and amino acid biosynthesis (Bray (1983) Nitrogen Metabolism in Plants. Longman, London); however, NADP+ IDH (EC 1.1.1.42) has recently been regarded as an alternative pathway when large quantities of 2-oxoglutarate are required (Chen et al. (1990a) Plant Physiol Biochem 28:141-145; Galvez et al. (1995) Plant Sci 105:1-14).
AND+ IDH is localized exclusively in the mitochondria in association with the TCA cycle. This enzyme has been purified from several nonphotosynthetic eukaryotes such as fungi (Keys et al. (1990) Bacteriol 172:4280-4287; Alvarez-Villafane et al. (1996) Biochemistry 35:4741-4752) and animals (Giorgio et al. (1970) J. Biol Chem 245:5469-5477), in which it appears to be a 300-kD octamer. AND-IDH cDNAs have been cloned from yeast (Cupp et al. (1991) J. Biol Chem 266: 22199-22205) and animals (Nichols et al. (1995) Biochem J 310:917-922). In these organisms, the enzyme is composed of two (yeast) or more (animals) different subunits encoded by different genes.
Accordingly, the availability of nucleic acid sequences encoding all or a portion of an isocitrate dehydrogenase would facilitate studies to better understand carbon and nitrogen metabolic pathways in plant cells and provide genetic tools to enhance or otherwise alter these pathways which in turn could provide mechanisms to modulate the citric acid cycle and possibly ammonia assemilation in plant cells. Additionally, the instant isocitrate dehydrogenase proteins can be used as a targets to facilitate design and/or identification of inhibitors of those enzymes that may be useful as herbicides.